2. Academic Validation
  3. Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression

Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression

  • BMC Cancer. 2023 Oct 30;23(1):1042. doi: 10.1186/s12885-023-11519-5.
Linghui Jia # 1,  Liting Liao # 1,  Yongshuai Jiang 1,  Xiangyu Hu 1,  Guotao Lu 2,  Weiming Xiao 2,  Weijuan Gong 1 2 3 4 5,  Xiaoqin Jia 6 7 8 9 10,  Jia Xiaoqin 1
Affiliations

Affiliations

  • 1 Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou, 225001, P. R. China.
  • 2 Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou, 225001, P. R. China.
  • 3 Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou, 225001, P. R. China.
  • 4 Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225001, P. R. China.
  • 5 Jiangsu Key Laboratory of Zoonosis, Yangzhou, 225001, P. R. China.
  • 6 Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou, 225001, P. R. China. xqjia@yzu.edu.cn.
  • 7 Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou, 225001, P. R. China. xqjia@yzu.edu.cn.
  • 8 Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou, 225001, P. R. China. xqjia@yzu.edu.cn.
  • 9 Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225001, P. R. China. xqjia@yzu.edu.cn.
  • 10 Jiangsu Key Laboratory of Zoonosis, Yangzhou, 225001, P. R. China. xqjia@yzu.edu.cn.
  • # Contributed equally.
PMID: 37904094 DOI: 10.1186/s12885-023-11519-5
Abstract

Adropin is encoded by the energy homeostasis-associated (ENHO) gene and widely present in liver, pancreas, heart, kidney, brain, and vascular tissues. Abnormal adropin is associated with metabolic, inflammatory, immune, and central nervous disorders. Whether adropin is involved in the development of colorectal Cancer (CRC) is still unclear. Here, decreased adropin expression of tumor-nest cells in advanced-stage CRC was demonstrated. Adropin expressed by carcinoma cells was negatively correlated with macrophage infiltration in the matrix of CRC tissues. However, tumor macrophages enhanced adropin expression and were positively correlated with tumor invasion and metastasis. ENHO gene transfection into colon Cancer (MC38) cells inhibited tumor growth in vivo, accompanying the increase of M1 macrophages. Treatment with low-dose adropin (< 100 ng/mL) on macrophages ex vivo directly increased mitochondrial Reactive Oxygen Species for inflammasome activation. Furthermore, ENHO-/- mice had less M1 macrophages in vivo, and ENHO-/- macrophages were inert to be induced into the M1 subset ex vivo. Finally, low-dose adropin promoted glucose utilization, and high-dose adropin enhanced the expression of CPT1α in macrophages. Therefore, variations of adropin level in carcinoma cells or macrophages in tumor tissues are differently involved in CRC progression. Low-dose adropin stimulates the antitumor activity of macrophages, but high-dose adropin facilitates the pro-tumor activity of macrophages. Increasing or decreasing the adropin level can inhibit tumor progression at different CRC stages.

Keywords

Adropin; Colorectal cancer; Inflammasome; Macrophage; mROS.

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